Skip to main content
SpringerLink
Log in

Analysis of the association of the G-7A polymorphism of the matrix Gla protein gene with ischemic atherothrombotic stroke in humans with its different risk factors

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

Abstract

The G-7A polymorphism (rs1800801) of the matrix Gla protein (MGP) gene was determined in 170 patients with ischemic atherothrombotic stroke (IATS) and 124 control persons. It was found that the distribution of the major allele homozygotes, heterozygotes, and minor allele homozygotes was 35.9, 48.8, and 15.3% in patients with IATS (in the control, 43.5, 50.0, and 6.5%; P = 0.051 by the χ2 test). Significant differences in the distribution of genotypes were revealed only in women (P = 0.022). The odds ratio (OR) for minor allele homozygotes (A/A) vs. major allele carriers (G/A + G/G) was 2.618 (P = 0.023), while in women it was equal to 6.645 (P = 0.015). In patients with the A/A genotype, the values of the blood coagulation parameters (prothrombin time) indicated increased their predisposition to hypercoagulability. The results obtained prove that the A/A variant of the MGP gene is associated with an increased risk of IATS in females of the Ukrainian population and may be related to blood hypercoagulability and formation of thrombi.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Allison, M.A. and Wright, C.M., Age and gender are the strongest clinical correlates of prevalent coronary calcification (R1), Int. J. Card., 2005, vol. 98, pp. 325–330.

    Article  Google Scholar 

  2. Detrano, R.C., Wong, N.D., Doherty, T.M., and Shavelle, R., Prognostic significance of coronary calcific deposits in asymptomatic high-risk subjects, Am. J. Med., 1997, vol. 102, pp. 344–349.

    Article  PubMed  CAS  Google Scholar 

  3. Fuessl, H.S., Schalzky, H., Schewe, S., et al., Zur pathogenese und lkinischen bedeutung der mnckebergschen mediaverkalkung, Klin. Wochenschr., 1985, vol. 63, pp. 211–216.

    Article  PubMed  CAS  Google Scholar 

  4. Iribarren, C., Sidney, S., Sternfeld, B., and Browner, W.S., Calcification of the aortic arch: risk factors and association with coronary heart disease stroke, and peripheral vascular disease, J. Am. Med. Assoc., 2000, vol. 283, pp. 2810–2815.

    Article  CAS  Google Scholar 

  5. Johnson, R.C., Leopold, J.A., and Loscalzo, J., Vascular calcification. pathobiological mechanisms and clinical implications, Circ. Res., 2006, vol. 99, pp. 1044–10159.

    Article  PubMed  CAS  Google Scholar 

  6. Lehto, S., Niskanen, L., Suhonen, M., et al., Medial artery calcification. a neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus, Arterioscler. Thromb. Vasc. Biol., 1996, vol. 16, pp. 978–988.

    Article  PubMed  CAS  Google Scholar 

  7. Wayhs, R., Zelinger, A., and Raggi, P., High coronary artery calcium scores pose and extremely elevated risk for hard events, J. Am. Col. Card, 2002, vol. 39, pp. 225–230.

    Article  Google Scholar 

  8. Price, P.A., Urist, M.R., and Otawara, Y., Matrix Gla protein, a new γ-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone, Biochem. Biophys. Res. Commun., 1983, vol. 117, pp. 765–771.

    Article  PubMed  CAS  Google Scholar 

  9. Fraser, J.D. and Price, P.A., Lung, heart, and kidney express high levels of mRNA for the vitamin k-dependent matrix Gla protein, J. Biol. Chem., 1988, vol. 263, pp. 11033–11036.

    PubMed  CAS  Google Scholar 

  10. Price, P.A. and Williamson, M.K., Primary structure of bovine matrix Gla protein, a new vitamin k-dependent bone protein, J. Biol. Chem., 1985, vol. 260, pp. 14971–14975.

    PubMed  CAS  Google Scholar 

  11. Cancela, L., Hsiehg, C.-L., Francket, U., and Price, P.A., Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene, J. Biol. Chem., 1990, vol. 265, pp. 15040–15048.

    PubMed  CAS  Google Scholar 

  12. Price, P.A., Faus, S.A., and Williamson, M.K., Warfarin-induced artery calcification is accelerated by growth and vitamin D, Arterioscler. Thromb. Vasc. Biol., 2000, vol. 20, pp. 317–327.

    Article  PubMed  CAS  Google Scholar 

  13. Proudfoot, D. and Shanahan, C.M., Molecular mechanisms mediating vascular calcification: role of matrix Gla protein, Nephrology (Carlton), 2006, vol. 11, pp. 455–461.

    Article  CAS  Google Scholar 

  14. Schurgers, L.J., Teunissen, K.J.F., Knapen, M.H.J., et al., Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein, Arterioscler. Thromb. Vasc. Biol., 2005, vol. 25, pp. 1629–1633.

    Article  PubMed  CAS  Google Scholar 

  15. Stanford, W., Coronary artery calcification as an indicator of preclinical coronary artery disease, Radiographics, 1999, vol. 19, pp. 1409–1419.

    PubMed  CAS  Google Scholar 

  16. Shanahan, C.M., Proudfoot, D., Tyson, K.L., et al., Expression of mineralization-regulating proteins in association with human vascular calcification, Z. Kardiol., 2000, vol. 89,suppl. 2, pp. 64–68.

    Google Scholar 

  17. Giachelli, C.M., Vascular calcification mechanisms, J. Am. Soc. Nephrol., 2004, vol. 15, pp. 2959–2964.

    Article  PubMed  Google Scholar 

  18. Herrmann, S.M., Whatling, C., Brand, E., et al., Polymorphisms of the human matrix Gla protein, MGP0 gene, vascular calcification, and myocardial infarction, Arterioscler. Thromb. Vasc. Biol., 2000, vol. 20, pp. 2386–2393.

    Article  PubMed  CAS  Google Scholar 

  19. Farzaneh-Far, A., Davies, J.D., Braam, L.A., et al., A polymorphism of the human matrix γ-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels, J. Biol. Chem., 2001, vol. 276, pp. 32466–32473.

    Article  PubMed  CAS  Google Scholar 

  20. Kobayashi, N., Kitazawa, R., Maeda, S., et al., T-138C polymorphism of matrix Gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification, Kobe J. Med. Sci., 2004, vol. 50, pp. 69–81.

    PubMed  CAS  Google Scholar 

  21. Brancaccio, D., Biondi, M.L., Gallieni, M., et al., Matrix Gla protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients, Am. J. Nephrol., 2005, vol. 25, pp. 548–552.

    Article  PubMed  CAS  Google Scholar 

  22. Taylor, B.C., Schreiner, P.J., Doherty, T.M., et al., Matrix Gla protein and osteopontin genetic associations with coronary artery calcification and bone density: the cardio study, Hum. Genet., 2005, vol. 116, pp. 525–528.

    Article  PubMed  CAS  Google Scholar 

  23. Crosier, M.D., Booth, S.L., Peter, I., et al., Matrix Gla protein polymorphisms are associated with coronary artery calcification, J. Nutr. Sci. Vitaminol., 2009, vol. 55, pp. 59–65.

    Article  PubMed  CAS  Google Scholar 

  24. Garbuzova, V.Yu., Gur’yanova, V.L., Parkhomenko, A.N., et al., The frequency of the allelic variants of the matrix Gla protein (MGP) gene in patients with acute coronary syndrome, Fiziol. Zh., 2011, vol. 57, pp. 16–24.

    CAS  Google Scholar 

  25. Adams, H.P., Bendixen, B.H., Kappelle, L.J., et al., Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment, Stroke, 1993, vol. 24, pp. 35–41.

    Article  PubMed  Google Scholar 

  26. Abedin, M., Tintut, Y., and Demer, L.L., Vascular calcification. Mechanisms and clinical ramifications, Arterioscler. Thromb. Vasc. Biol., 2004, vol. 24, pp. 1161–1170.

    Article  PubMed  CAS  Google Scholar 

  27. Doherty, T.M., Fitzpatrick, L.A., Inoue, D., et al., Molecular, endocrine, and genetic mechanisms of arterial calcification, Endocrine Rev., 2004, vol. 25, pp. 629–672.

    Article  CAS  Google Scholar 

  28. Guzman, R.J., Clinical, cellular, and molecular aspects of arterial calcification, J. Vasc. Surg., 2007, vol. 45, Suppl. A, pp. A57–A63.

    Article  Google Scholar 

  29. Jayalath, R.W., Mangan, S.H., and Golledge, J., Aortic calcification, Eur. J. Endovasc. Surg., 2005, vol. 30, pp. 476–488.

    Article  CAS  Google Scholar 

  30. Johnson, R.C., Leopold, J.A., and Loscalzo, J., Vascular calcification. pathobiological mechanisms and clinical implications, Circ. Res., 2006, vol. 99, pp. 1044–1059.

    Article  PubMed  CAS  Google Scholar 

  31. Braam, L.A., Dissel, P., Gijsbers, B.L., et al., Assay for human matrix Gla protein in serum. Potential applications in the cardiovascular fields, Arterioscler. Thromb. Vasc. Biol., 2000, vol. 20, pp. 1257–1261.

    Article  PubMed  CAS  Google Scholar 

  32. Jono, S., Vermeer, C., Dissel, P., et al., Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography, Thromb. Haemost., 2004, vol. 91, pp. 790–794.

    PubMed  CAS  Google Scholar 

  33. Donnell, C.J., Kyla, SheaM., Price, P.A., et al., Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification, Arteriosckler. Thromb. Vasc. Biol., 2006, vol. 26, pp. 2769–2774.

    Article  Google Scholar 

  34. Bos, D., Ikram, M.A., Elias-Smale, S.E., et al., Calcification in major vessel beds relates to vascular brain disease, Arterioscler. Thromb. Vasc. Biol., 2011, vol. 31, pp. 2331–2337.

    Article  PubMed  CAS  Google Scholar 

  35. Acar, A., Cevik, M.U., Arkanoglu, A., et al., Serum levels of calcification inhibitors in patients with intracerebral hemorrhage, Int. J. Neurosci., 2012, vol. 122, pp. 227–232.

    Article  PubMed  CAS  Google Scholar 

  36. Kubo, M., Genetic risk factors of ischemic stroke identified by a genome-wide association study, Brain Nerve, 2008, vol. 60, pp. 1339–1346.

    PubMed  CAS  Google Scholar 

  37. Debette, S. and Sechardi, S., Genetics of atherothrombotic and lacunare stroke, Circ. Cardiovasc. Gen., 2009, vol. 2, pp. 191–198.

    Article  CAS  Google Scholar 

  38. Matarin, M., Brown, W.M., Dena, H., et al., Candidate gene polymorphisms for ischemic stroke, Stroke, 2009, vol. 40, pp. 3436–3442.

    Article  PubMed  CAS  Google Scholar 

  39. Wang, X., Cheng, S., Brophy, V.H., et al., A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients, Stroke, 2009, vol. 40, pp. 683–695.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sumy State University, Sumy, Ukraine

    A. V. Ataman, V. Yu. Garbusova, Yu. A. Ataman & O. I. Matlaj

  2. Kursk State Medical University, Kursk, Russia

    A. V. Polonikov

Authors
  1. A. V. Ataman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. V. Polonikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Yu. Garbusova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yu. A. Ataman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O. I. Matlaj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. V. Ataman.

Additional information

Original Ukrainian Text © A.V. Ataman, A.V. Polonikov, V.Yu. Garbusova, Yu.A. Ataman, O.I. Matlaj, 2013, published in Tsitologiya i Genetika, 2013, Vol. 47, No. 5, pp. 33–40.

About this article

Cite this article

Ataman, A.V., Polonikov, A.V., Garbusova, V.Y. et al. Analysis of the association of the G-7A polymorphism of the matrix Gla protein gene with ischemic atherothrombotic stroke in humans with its different risk factors. Cytol. Genet. 47, 287–293 (2013). https://doi.org/10.3103/S0095452713050034

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452713050034

Kewords

Search

Navigation